The premise, that the concentration of fluorophosphate-sensitive carboxylesterase sites in the liver is quantitatively related to the amount of endoplasmic reticulum in hepatocytes, will be tested. For this purpose correlated electron microscope autoradiographic, morphometric and biochemical analyses will be made on developing and mature liver from normal and barbiturate treated mice. Tritriated diisopropylphosphorofluoridate (DFP) will be used to label the fluorophosphate-sensitive sites. The site (or sites) of formation, turnover rate and translocation pathway of carboxylesterase molecules and endoplasmic reticulum membrane will be identified in hepatocytes in culture. Combined morphometric and autoradiographic measurements of fluorophosphate-sensitive esterase sites in human liver biopsy specimens will be made and used as an aid in diagnosis of liver diseases, to detect incipient alterations in liver function and for assessing the status of hepatocytes in patients recovering from impaired liver function. BIBLIOGRAPHIC REFERENCES: Jacob, J. and Budd, G.C. Application of electron microscope autoradiography to the localization of enzymatic activity. In Electron Microscopy of Enzymes: Principles and Methods (Ed. M. A. Hayat) Vol. 4. Van Nostrand Reinhold Co., N.Y. (1975). Chakraborty, J., Budd, G.C. and Nelson, L. Fine structural localization of cholinesterases in the reproductive tract of the male mouse. Biology of Reproduction 13, 397-407 (1975).